Absorbable polymers and medical devices made from such polymers are known in the art. Conventional absorbable polymers include polylactic acid, poly(p-dioxanone), polyglycolic acid, co-polymers of lactide, glycolide, p-dioxanone, trimethylene carbonate, ε-caprolactone, in various combinations, etc. The chemistry of absorbable polymers is designed such that the polymers breakdown in vivo, for example by hydrolysis, and the byproducts metabolized or otherwise excreted from the patient's body. The advantages of utilizing implantable medical devices made from absorbable polymers are numerous and include, for example, eliminating the need for additional surgeries to remove an implant after it serves its function. In the case of a wound closure function, when a “temporary presence” of the implant is desired, ideally support can be provided until the tissue heals.
Absorbable is meant to be a generic term, which may also include bioabsorbable resorbable, bioresorbable, degradable or biodegradable.
The absorbable polymers conventionally used to manufacture medical devices have been on occasion polymeric blends of absorbable polymers and co-polymers engineered to provide specific characteristics and properties to the manufactured medical device, including absorption rates, mechanical property (e.g., breaking strength) retention post-implantation, and dimensional stability, etc.
There are many conventional processes used to manufacture medical devices from absorbable polymers and polymer blends. The processes include injection molding, solvent casting, extrusion, machining, cutting and various combinations and equivalents. A particularly useful and common manufacturing method is thermal forming using conventional injection molding processes and extrusion processes.
The retention of mechanical properties post-implantation is often a very important feature of an absorbable medical device. The device must retain mechanical integrity until the tissue has healed sufficiently. In some bodily tissues, healing occurs more slowly, requiring an extended retention of mechanical integrity. This is often associated with tissue that has poor vascularization. Likewise there are other situations in which a given patient may be prone to poor healing: e.g., the diabetic patient. There are however many situations in which rapid healing occurs, which require the use of fast absorbing medical devices such as sutures; this is often associated with excellent vascularization. Examples of where such fast absorbing sutures can be used include certain pediatric surgeries, oral surgery, repair of the peritoneum after an episiotomy and superficial wound closures.
When rapid healing occurs, the mechanical retention profile of the medical device could reflect a more rapid loss in properties. Concomitant with this is the rate of absorption (bioabsorption or resorption), that is, the time required for the medical device to disappear from the surgical site.
One method that has been exploited to achieve the rapid loss of mechanical properties is the use of pre-hydrolysis and/or gamma irradiation. For instance Hinsch et al., in EP 0 853 949 B1, describe a process for reducing the resorption period of hydrolyzable resorbable surgical suture material, wherein the surgical suture material is incubated in a hydrolysis buffer, having an index of pH in the range from 4 to 10, for a period in the range from 10 hours to 100 hours at a temperature in the range from 30° C. to 65° C.
In order to shorten the absorption period of absorbable suture material it is also known to irradiate the suture material during the manufacture, e.g., by means of Co-60 gamma irradiation. Such an irradiation process produces defects in the polymer structure of the suture material, resulting in an accelerated decrease of the tensile strength and a shortened absorption period in vivo after implantation of the suture material. To use gamma irradiation in a manufacturing environment in order to reliably adjust in vivo absorption times and control post-implantation mechanical property loss is often difficult due to a variety of reasons. These reasons include the high precision required, and, the unintended damage to other important properties such as discoloration.
It is well known, however, that such treatments of pre-hydrolysis and gamma irradiation may have a negative effect on the mechanical properties of the device. Consequently, and for example, sutures that are touted as fast absorbing are often lower in initial strength than their standard absorbing suture counterparts.
In certain surgical procedures, the mechanical properties, particularly the tensile strength, of the wound closure device are clinically very important; in these wound closure devices, such as sutures, high strength is generally preferred. Commercially available braided fast absorbing suture sold by ETHICON, Inc., Somerville, N.J. 08876, and known as VICRYL RAPIDE™ (polyglactin 910) Suture exhibits a tensile strength of about 60 percent of the standard absorbing counterpart, Coated VICRYL™ (polyglactin 910) Suture.
There is a continuing need in this art for novel medical devices that lose their mechanical properties quickly and are absorbed rapidly, but which still provide high initial mechanical properties approaching those exhibited by their standard absorbing counterparts.
There have been attempts in the prior art to address the problem of rapid absorption. Rose and Hardwick in U.S. Pat. No. 7,524,891 describe the addition of certain carboxylic acids and their derivatives and anhydrides to poly(lactic acid) to make homogeneous blends, which exhibit a more rapid absorption. It should be noted that that they limit the amount of the additive to 10 weight percent. They clearly describe a system in which the additive is admixed throughout and is not reactive with the poly(lactic acid) so as to create a derivative.
There have been attempts in the prior art to address the problem of improved strength. For instance, Brown in US Patent Application Publication No. 2009/0274742 A1, entitled “Multimodal High Strength Devices And Composites”, (hereinafter referred to as “'742”) discloses an oriented implantable biodegradable multimodal device comprising a blend of a first polymer component having a first molecular weight together with at least a second polymer component having a molecular weight which is less than that of the first component, wherein polymer components within the blend are in uniaxial, biaxial or triaxial orientation. Brown speaks of achieving higher mechanical properties in blends of high molecular weight polylactide (e.g., IV=4.51 dL/g) with much lower molecular weight versions of this polymer (Mw=5,040 Da, Mn=3,827 Da), but only shows an increase in modulus and no increase in maximum stress. Additionally, Brown in '742 mentions a faster rate of absorption as compared to the high molecular weight polylactide when an additive is admixed in an amount of not more than 10% by weight of the polymer components.
A bimodal bioabsorbable polymer composition is disclosed in US Patent Application Publication US 2007/0149640 A1. The composition includes a first amount of a bioabsorbable polymer polymerized so as to have a first molecular weight distribution and a second amount of said bioabsorbable polymer polymerized so as to have a second molecular weight distribution having a weight average molecular weight between about 20,000 to about 50,000 Daltons. The weight average molecular weight ratio of said first molecular weight distribution to said second molecular weight distribution is at least about two to one, wherein a substantially homogeneous blend of said first and second amounts of said bioabsorbable polymer is formed in a ratio of between about 50/50 to about 95/5 weight/weight percent. Also disclosed are a medical device and a method of making a medical device.
In US 2009/0118241 A1, a bimodal bioabsorbable polymer composition is disclosed. The composition includes a first amount of a bioabsorbable polymer polymerized so as to have a first molecular weight distribution and a second amount of said bioabsorbable polymer polymerized so as to have a second molecular weight distribution having a weight average molecular weight between about 10,000 to about 50,000 Daltons. The weight average molecular weight ratio of said first molecular weight distribution to said second molecular weight distribution is at least about two to one, wherein a substantially homogeneous blend of said first and second amounts of said bioabsorbable polymer is formed in a ratio of between about 50/50 to about 95/5 weight/weight percent. Also disclosed are a medical device, a method of making a medical device and a method of melt blowing a semi-crystalline polymer blend.
Even though such polymer blends are known, there is a continuing need in this art for novel absorbable polymeric materials having precisely controllable absorption rates, that provide a medical device with improved characteristics including stiffness, retained strength in vivo (in situ), dimensional stability, absorbability in vivo, and manufacturability; there is a particular need for accelerated absorption and accelerated mechanical property loss post-implantation while still exhibiting high initial mechanical properties.